Immune disruption seen more than 9 years prior to CLL diagnosis:

NEW YORK (Reuters Health) - Patients who develop chronic lymphocytic leukemia (CLL) often have evidence of immune disruption, in the form of B-cell clones, years prior to diagnosis, according to results of a study presented Monday at the American Association for Cancer Research annual meeting in Denver.

"Our finding that CLL is commonly preceded by altered immune status provides a rationale for future investigations to assess if pre-diagnostic immunodeficiency has an impact on CLL prognosis," the study team concludes in a meeting abstract.

"The cause of CLL is completely unknown," Dr. Neil Caporaso, of the National Cancer Institute, Rockville, Maryland, noted at an AACR briefing Monday. "We know nothing about the extrinsic carcinogens that cause CLL and, in spite of three linkage studies...we don't know a major gene that causes CLL."

Earlier this year in The New England Journal of Medicine, the researchers reported that 44 of 45 patients with CLL had small numbers of B-cell clones in the peripheral blood -- a condition referred to as monoclonal B-cell lymphocytosis -- up to 7 years prior to the diagnosis of CLL.

Today at AACR, Dr. Caporaso reported results of an analysis of pre-diagnostic stored serum samples from 109 patients with CLL.

"Forty-one of 109 patients (38%) had abnormal free light chain proteins in their blood as far as 9.8 years prior to diagnosis," Dr. Caporaso reported. This is evidence of an early immune disruption and this is the first prospective study to show this, he added.

By contrast, only a small percentage of patients (13.1%) had hypogammaglobulinemia -- an indication of impaired immune function that is common in CLL.

The current study, Dr. Caporaso said, "gives us a clue to the etiology of CLL, because what we have is people walking around with these abnormal clones, or abnormal collections of cells, and apparently these cells are cranking out proteins years before people get CLL."

Going forward, he said, "we can study what causes people to get these abnormalities and, more importantly, what causes somebody to progress from having a relatively benign protein abnormality to developing leukemia. We can search for environmental agents and genes that could cause this next step."

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